From September 2009 to July 2010 the CCR-SF has sequenced more than 500 samples for 28 different NCI principal investigators, generated 927 GB of mappable data, and has completed 62 projects. Sample types that have been successfully sequenced include: genomic DNA, Chromatin Immuno-Precipitated DNA (ChIP), 4C DNA, mRNA, short hairpin DNA, microRNA and Bisulfite samples. The labor intensive library preparation step is the major workflow bottle neck. To reduce library preparation costs and increase library preparation throughput and the efficiency of laboratory operations, the CCR-SF team has implemented Beckmans SPRIworks Fragment Library System (SPRI-TE). The SPRI-TE has the capability to produce three times the number of libraries prepared by a technician, uses a tightly controlled micro fluidics system to reduce manual liquid transfer variability, and the reagent costs are currently at or below the cost of the Illumina library preparation reagents before optimization. CCR-SF bioinformatics has implemented standard analyses on all applications. These analyses have been incorporated into an automation pipeline providing additional time to bioinformatics staff for optimizing the data quality and automation process. CCR-SF bioinformatics takes all new customers through an Introduction to Illumina session complete with a document for future reference. This course has been given to 23 NCI laboratories. The CCR-SF Quality Management team has implemented a robust QC workflow to help identify potential failures as early as possible. Of approximately 700 samples that have met acceptance criteria, only 28 samples (4%) failed to pass library construction, indicating a robust and highly predictive sample QC process.